The etiology of multiple sclerosis: temporal-spatial clustering indicating two environmental exposures before onset

Studies in the Orkney and Shetland Islands have demonstrated the highest rates of multiple sclerosis (MS) recorded. Accumulated evidence suggests that an environmental factor is paramount in etiology. The role of an environmental exposure (infectious or toxic) is confirmed in this study by the demonstration in Orkney of clustering of cases in time and space. Lifetime data showed temporal-spatial clustering of MS patients (1) at least 21 years prior to onset, and (2) just prior to onset. Each of the two time clusters occurred on three separate islands. No clustering was seen at birth, by chronological age, or by schooling. Clustering was not demonstrated in Shetland. Previous efforts to demonstrate clustering may have failed because of lack of specificity of the data or inappropriate methodology. These data indicate that not one but two environmental factors play a role in the etiology of MS, representing exposures to two different environmental insults, or exposure twice to the same insult, prior to onset of MS.